高脂饮食诱导肥胖引起铁缺乏的机制

MECHANISMS OF IRON DEFICIENCY INDUCED BY HIGH-FAT DIET IN MICE

目的探讨高脂饮食诱导的肥胖引起铁缺乏的原因。方法利用高脂饮食16w建立C57BL/6J小鼠肥胖模型,火焰原子吸收法检测肝脏铁水平,RT-PCR检测铁调素(hepcidin)与炎症因子的基因表达,Western blotting检测肝、脾、十二指肠铁代谢相关蛋白的表达。结果与低脂饮食相比,高脂饮食的小鼠存在更高的体质量和更低水平的总铁、游离铁和铁蛋白(ferritin),而肝脏炎症因子白介素-6(IL-6)、白介素1β(IL-1β)、单核细胞趋化因子(MCP-1)及铁调素(hepcidin)表达增加,肝、脾、十二指肠的膜铁输出蛋白(ferroportin)表达下降。同时,高脂饮食的小鼠十二指肠细胞色素b(Dcytb)与二价金属离子转运蛋白1(DMT1)低表达,肝脏DMT1高表达。结论高脂模型下,炎症对肝hepcidin诱导及肠Dcytb下调,可能共同影响十二指肠铁的吸收而导致肥胖小鼠铁缺乏。

Objective To explore the potential mechanisms involved in iron deficiency induced by a high-fat diet in mice. Methods C57BL/6J mice were employed to establish obesity model through fed a high-fat diet （HFD） for 16 weeks. Hepatic iron levels were detected by flame atomic absorption spectrometry. The expression of mRNA/proteins associated with iron metabolism were measured by real-time PCR/western blot. Results Compared with the low-fat diet （LFD）, HFD induced a significantly higher body weight gain, in parallel with a lower hepatic total iron, labile iron pool （LIP）, ferritin, but an increased hepatic mRNA expression of hepcidin, inflammatory factors, including IL-6, IL-1β and MCP-1. In addition, the protein expression of ferroportin was significantly decreased in the liver, spleen, duodenum of HFD-fed mice. Moreover, HFD significantly decreased the duodenal protein expression of divalent metal transporter 1（DMT1） and cytochrome b （Dcytb） and increased hepatic protein expression of DMT1 in comparison with LFD. Conclusion Inflammation-induced high expression of hepcidin and suppressed expression of Dcytb in duodenal may collectively contribute to iron deficiency in mice fed a HFD.